Gut microbiota perturbations in response to SARS-CoV-2 and survival outcomes in patients with cancer.

Abstract

178 Background: The gut microbiota plays a critical role in immune function, but in diseases such as cancer, dysbiosis may increase vulnerability to external factors like viral infections. In this study, we investigated the impact of gut microbiota in relation to SARS-CoV-2 infection in cancer patients. Methods: Stools collected at recruitment underwent shotgun metagenomic sequencing and inflammatory cytokine profiling using ELISA. Taxonomy data were correlated with infection status, disease severity and mortality. All analyses were adjusted for age, sex, smoking status, tumor type, stage at COVID-19 diagnosis, comorbidities, and vaccination. Results: A total of 195 patients with solid tumors (colon=60, breast=43, miscellaneous=92) were prospectively enrolled. SARS-CoV-2-infected cancer patients (n=98) showed reduced α-diversity (Shannon and Chao1 indexes, p=0.002) and a distinct microbial composition (p=0.004) with Enterococcus spp. enrichment ( E.A avium, E.B faecium, E. faecalis ) compared to non-infected patients (n=97). Hospitalized patients due to severe SARS-CoV-2 infection exhibited depletion of several commensal species including Eubacterium spp. and Lachnospira spp., which were positively correlated with gut immune response assessed by stool cytokines. In an adjusted logistic model of overall survival, SARS-CoV-2 infection was significantly associated to higher all-cause mortality (OR=4.56; 95%CI: 2.16–10.03; p<0.0001). Forty-four taxa (32 depleted and 12 enriched) could differentiate deceased vs alive patients, independently of SARS-CoV-2 infection status. These severity-related microbiota composition correlated with the magnitude of systemic inflammatory response with increased concentration of blood C reactive protein, lactate dehydrogenase, and lymphopenia with depletion of commensals. Conclusions: Depletion of protective gut commensals and enrichment of pathogens may impair immune sensing and response to viral infections ultimately contributing to the hyperinflammatory state and lymphodepletion linked with severe disease and mortality. The lack of cohort-specific taxa suggests that the higher mortality induced by SARS-CoV-2 in cancer patients may be driven by a pre-existing dysbiosis.